Ecotoxicology and Environmental Safety (Feb 2024)

GCF2 mediates nicotine-induced cancer stemness and progression in hepatocellular carcinoma

  • Jinping Li,
  • Dayun Tuo,
  • Tan Cheng,
  • Zhenyan Deng,
  • Jinfeng Gan

Journal volume & issue
Vol. 271
p. 115952

Abstract

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Cigarette smoking is one of the most impactful behavior-related risk factors for multiple cancers including hepatocellular carcinoma (HCC). Nicotine, as the principal component of tobacco, is not only responsible for smoking addiction but also a carcinogen; nevertheless, the underlying mechanisms remain unclear. Here we report that nicotine enhances HCC cancer stemness and malignant progression by upregulating the expression of GC-rich binding factor 2 (GCF2), a gene that was revealed to be upregulated in HCC and whose upregulation predicts poor prognosis, and subsequently activating the Wnt/ꞵ-catenin/SOX2 signaling pathway. We found that nicotine significantly increased GCF2 expression and that silencing of GCF2 reduced nicotine-induced cancer stemness and progression. Mechanistically, nicotine could stabilize the protein level of GCF2, and then GCF2 could robustly activate its downstream Wnt/β-catenin signaling pathway. Taken together, our results thus suggest that GCF2 is a potential target for a therapeutic strategy against nicotine-promoted HCC.

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